We are continuing to probe the molecular basis of immune recognition through the application of modern techniques of experimental cellular immunology to the genetically defined murine model. The extremely well-characterized protein antigen, hen egg-white lysozyme (HEL), other avian and mammalian lysozymes, peptide fragments of HEL, specifically derivatized HEL and synthetic peptides related to HEL, are all utilized in this study. At each level of recognition there appears to be severe immune focusing to a highly restricted region of HEL which, however, is different for each cell type: B cells, helper T cells and suppressor T cells. In addition, the response is dominated by a single public idiotype IdXL. At the B cell level, we plan to explore more extensively the early transient recognition by B cells of an epitope including the three N-terminal amino acids of HEL which normally appears obligatory for subsequent recognition of other epitopes by B cells. In particular, we shall attempt to disrupt this ordered read-out by a number of alternative modes of immunization and pretreatments. We have shown that the ultimate epitopes recognized by B cells seem confined to a single face of HEL and we plan more careful definition of this restriction. We have established a library of HELspecific T-cell clones. We shall explore the relation of proliferation and help and the interaction of T cells with each other through the use of in vivo assays in use in our laboratory. The nature of suppression in the HEL system will continue to be studied with emphasis on the restricted specificity of T suppressor cells and on their role in tolerance and in idiotypic regulation. The nature of IdXL in molecular terms will continue to be studied through analysis of monoclonal antibodies and the DNA of hybridomas giving rise to them. We also plan to expand studies on the interactions of other idiotypes with IdXL in an attempt to gain insight into the workings of immune regulatory networks.